H Phillip Koeffler, M.D.

Work Address:
8700 Beverly Blvd., #BM1-109 Cedars Sinai Medical Center
Los Angeles, CA 90048
CA

Affiliations
Affiliations
Professor, Medicine, Hematology Oncology
Member, JCCC Gene Regulation Program Area
Biography

Having developed a program in breast cancer research, Dr. Koeffler is looking at the molecular causes and novel forms of therapy of the disease. He has secured NIH grant and US Army grant funding for breast cancer. Dr. Koeffler has developed a program in prostate cancer research and is looking at novel forms of therapy. He has begun a clinical trial of 9-cis retinoic acid in the disease. He has secured NIH funding as wellas private philanthropic sources for prostate cancer. Leukemias, preleukemias and lymphomas: Studying the basic biology of these diseases and developing novel forms of therapy including vaccines. He has NIH funding that is used for this research. Dr. Koeffler has cloned a pivotal hematopoietic control gene known asC\EBPs, and now making transgenic and "knockout" mice to define the in vivo activities of this gene. He anticipates writing a major NIH grant for this work. Program of cloning new genes: Dr. Koeffler has recently cloned a cyclinA1 gene and a protein processing gene using molecular biology and genetic techniques, and he is now defining the biology of these genes and their implications to cancer development. He has established a research team that uses computers, data banks and gene libraries to clone rapidly novel, interesting genes. Identification of novel tumor suppressor genes using extensive tumor DNA banks from over twenty tumor types with matched normal control DNA from the same individual and using over 300 microsatellites. Dr. Koeffler’s group is sublocalizing the site of tumor suppressor genes that are mutated in a variety of cancers. This study is funded in part by the Concern Foundation.

Publications
Hofmann WK, Koeffler HP Myelodysplastic syndrome. Annu Rev Med. 2005; 56: 1-16.
Williamson EA, Williamson IK, Chumakov AM, Friedman AD, Koeffler HP CCAAT/enhancer binding protein epsilon: changes in function upon phosphorylation by p38 MAP kinase. Blood. . 2005; 105(10): 3841-7.
Kumagai T, Shih LY, Hughes SV, Desmond JC, O'Kelly J, Hewison M, Koeffler HP 19-Nor-1,25(OH)2D2 (a novel, noncalcemic vitamin D analogue), combined with arsenic trioxide, has potent antitumor activity against myeloid leukemia. Cancer research. . 2005; 65(6): 2488-97.
Mhawech P, Benz A, Cerato C, Greloz V, Assaly M, Desmond JC, Koeffler HP, Lodygin D, Hermeking H, Herrmann F, Schwaller J Downregulation of 14-3-3sigma in ovary, prostate and endometrial carcinomas is associated with CpG island methylation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. . 2005; 18(3): 340-8.
Gery S, Tanosaki S, Hofmann WK, Koppel A, Koeffler HP C/EBPdelta expression in a BCR-ABL-positive cell line induces growth arrest and myeloid differentiation. Oncogene. . 2005; 24(9): 1589-97.
Yin D, Zhou H, Kumagai T, Liu G, Ong JM, Black KL, Koeffler HP Proteasome inhibitor PS-341 causes cell growth arrest and apoptosis in human glioblastoma multiforme (GBM). Oncogene. . 2005; 24(3): 344-54.
Kawabata H, Fleming RE, Gui D, Moon SY, Saitoh T, O'Kelly J, Umehara Y, Wano Y, Said JW, Koeffler HP Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood. . 2005; 105(1): 376-81.
Yang Y, Takeuchi S, Tsukasaki K, Yamada Y, Hata T, Mori N, Fukushima A, Seo H, Koeffler HP, Taguchi H Methylation analysis of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma. Leukemia research. . 2005; 29(1): 47-51.
Chien W, Kumagai T, Miller CW, Desmond JC, Frank JM, Said JW, Koeffler HP Cyr61 suppresses growth of human endometrial cancer cells. The Journal of biological chemistry. . 2004; 279(51): 53087-96.
Takai N, Kawamata N, Gui D, Said JW, Miyakawa I, Koeffler HP Human ovarian carcinoma cells: histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer. . 2004; 101(12): 2760-70.
Gery S, Park DJ, Vuong PT, Chih DY, Lemp N, Koeffler HP Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes. Blood. . 2004; 104(13): 3911-7.
Worch J, Tickenbrock L, Schwable J, Steffen B, Cauvet T, Mlody B, Buerger H, Koeffler HP, Berdel WE, Serve H, Muller-Tidow C The serine-threonine kinase MNK1 is post-translationally stabilized by PML-RARalpha and regulates differentiation of hematopoietic cells. Oncogene. 2004; 23(57): 9162-72.
Chih DY, Park DJ, Gross M, Idos G, Vuong PT, Hirama T, Chumakov AM, Said J, Koeffler HP Protein partners of C/EBPepsilon. Experimental hematology. . 2004; 32(12): 1173-81.
Kawabata H, Tong X, Kawanami T, Wano Y, Hirose Y, Sugai S, Koeffler HP Analyses for binding of the transferrin family of proteins to the transferrin receptor 2. British journal of haematology. . 2004; 127(4): 464-73.
Jones LC, Tefferi A, Idos GE, Kumagai T, Hofmann WK, Koeffler HP RARbeta2 is a candidate tumor suppressor gene in myelofibrosis with myeloid metaplasia. Oncogene. . 2004; 23(47): 7846-53.
Konopleva M, Elstner E, McQueen TJ, Tsao T, Sudarikov A, Hu W, Schober WD, Wang RY, Chism D, Kornblau SM, Younes A, Collins SJ, Koeffler HP, Andreeff M Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. Molecular cancer therapeutics. . 2004; 3(10): 1249-62.
Morosetti R, Servidei T, Mirabella M, Rutella S, Mangiola A, Maira G, Mastrangelo R, Koeffler HP The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines. International journal of oncology. . 2004; 25(2): 493-502.
Matsushita C, Yang Y, Takeuchi S, Matsushita M, Van Dongen JJ, Szczepanski T, Bartram CR, Seo H, Koeffler HP, Taguchi H Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia. Oncology reports. . 2004; 12(1): 97-9.
Ikezoe T, Tanosaki S, Krug U, Liu B, Cohen P, Taguchi H, Koeffler HP Insulin-like growth factor binding protein-3 antagonizes the effects of retinoids in myeloid leukemia cells. Blood. . 2004; 104(1): 237-42.
Takeuchi S, Takeuchi N, Tsukasaki K, Yang Y, Fermin AC, Tomonaga M, Miller CW, Seo H, Koeffler HP Methylenetetrahydrofolate reductase genotype does not play a role in adult T-cell leukemia/lymphoma pathogenesis among human T-lymphotrophic virus type 1 carriers. Leuk Res. 2004; 28(10): 1039-41.
Servidei T, Morosetti R, Ferlini C, Cusano G, Scambia G, Mastrangelo R, Koeffler HP The cellular response to PPARgamma ligands is related to the phenotype of neuroblastoma cell lines. Oncology research. . 2004; 14(7-8): 345-54.
Muller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Kohler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert SW, Koeffler HP, Berdel WE, Serve H Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol. 2004; 24(7): 2890-904.
Takeuchi S, de Vos S, Takeuchi N, Fermin AC, Grogan TM, Seo H, Said JW, Koeffler HP Allelic loss during progression of follicular lymphoma. Leukemia research. . 2004; 28(6): 567-9.
Ikezoe T, Yang Y, Taguchi H, Koeffler HP JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA). British journal of cancer. . 2004; 90(10): 2017-24.
Tsukasaki K, Tanosaki S, DeVos S, Hofmann WK, Wachsman W, Gombart AF, Krebs J, Jauch A, Bartram CR, Nagai K, Tomonaga M, Said JW, Koeffler HP Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays. International journal of cancer. Journal international du cancer. . 2004; 109(6): 875-81.
Chumakov AM, Kubota T, Walter S, Koeffler HP Identification of murine and human XCP1 genes as C/EBP-epsilon-dependent members of FIZZ/Resistin gene family. Oncogene. 2004; 23(19): 3414-25.
Ikezoe T, Saito T, Bandobashi K, Yang Y, Koeffler HP, Taguchi H HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2. Molecular cancer therapeutics. . 2004; 3(4): 473-9.
Yin D, Xie D, De Vos S, Liu G, Miller CW, Black KL, Koeffler HP Imprinting status of DLK1 gene in brain tumors and lymphomas. International journal of oncology. . 2004; 24(4): 1011-5.
Xie D, Yin D, Tong X, O'Kelly J, Mori A, Miller C, Black K, Gui D, Said JW, Koeffler HP Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways. Cancer research. . 2004; 64(6): 1987-96.
Xie D, Yin D, Wang HJ, Liu GT, Elashoff R, Black K, Koeffler HP Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas. Clinical cancer research : an official journal of the American Association for Cancer Research. . 2004; 10(6): 2072-81.
Kumagai T, Ikezoe T, Gui D, O'Kelly J, Tong XJ, Cohen FJ, Said JW, Koeffler HP RWJ-241947 (MCC-555), a unique peroxisome proliferator-activated receptor-gamma ligand with antitumor activity against human prostate cancer in vitro and in beige/nude/ X-linked immunodeficient mice and enhancement of apoptosis in myeloma cells induced by arsenic trioxide. Clinical cancer research : an official journal of the American Association for Cancer Research. . 2004; 10(4): 1508-20.
Gery S, Gombart AF, Fung YK, Koeffler HP C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis. Blood. . 2004; 103(3): 828-35.
Takai N, Desmond JC, Kumagai T, Gui D, Said JW, Whittaker S, Miyakawa I, Koeffler HP Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin Cancer Res. 2004; 10(3): 1141-9.
Shiohara M, Gombart AF, Sekiguchi Y, Hidaka E, Ito S, Yamazaki T, Koeffler HP, Komiyama A Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. Journal of leukocyte biology. . 2004; 75(2): 190-7.
Lee KW, Liu B, Ma L, Li H, Bang P, Koeffler HP, Cohen P Cellular internalization of insulin-like growth factor binding protein-3: distinct endocytic pathways facilitate re-uptake and nuclear localization. The Journal of biological chemistry. . 2004; 279(1): 469-76.
Rummel MJ, de Vos S, Hoelzer D, Koeffler HP, Hofmann WK Altered apoptosis pathways in mantle cell lymphoma. Leukemia & lymphoma. . 2004; 45(1): 49-54.
Tavor S, Park DJ, Gery S, Vuong PT, Gombart AF, Koeffler HP Restoration of C/EBPalpha expression in a BCR-ABL+ cell line induces terminal granulocytic differentiation. The Journal of biological chemistry. . 2003; 278(52): 52651-9.
Ikezoe T, Yang Y, Heber D, Taguchi H, Koeffler HP PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock. Molecular pharmacology. . 2003; 64(6): 1521-9.
Park DJ, Vuong PT, de Vos S, Douer D, Koeffler HP Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays. Blood. . 2003; 102(10): 3727-36.
Ikezoe T, Chen SS, Yang Y, Heber D, Taguchi H, Koeffler HP PC-SPES: Molecular mechanism to induce apoptosis and down-regulate expression of PSA in LNCaP human prostate cancer cells. International journal of oncology. . 2003; 23(5): 1461-70.
Takeuchi S, Seriu T, van Dongen JJ, Szczepanski T, Tsukasaki K, Takeuchi N, Fermin AC, Seo H, Bartram CR, Koeffler HP Allelotype analysis in relapsed childhood acute lymphoblastic leukemia. Oncogene. 2003; 22(44): 6970-6.
Ikezoe T, Chen SS, Tong XJ, Heber D, Taguchi H, Koeffler HP Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells. International journal of oncology. . 2003; 23(4): 1187-93.
Ikezoe T, Chen S, Saito T, Asou H, Kyo T, Tanosaki S, Heber D, Taguchi H, Koeffler HP PC-SPES decreases proliferation and induces differentiation and apoptosis of human acute myeloid leukemia cells. International journal of oncology. . 2003; 23(4): 1203-11.
Uehara E, Takeuchi S, Tasaka T, Matsuhashi Y, Yang Y, Fujita M, Tamura T, Nagai M, Koeffler HP Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia. International journal of oncology. . 2003; 23(3): 693-6.
Ikezoe T, Takeuchit S, Komatsu N, Okada M, Fukushima A, Ueno H, Koeffler HP, Taguchi H Identification of a new GLC1A mutation in a sporadic, primary open-angle glaucoma in Japan. International journal of molecular medicine. . 2003; 12(2): 259-61.
Chien W, Tidow N, Williamson EA, Shih LY, Krug U, Kettenbach A, Fermin AC, Roifman CM, Koeffler HP Characterization of a myeloid tyrosine phosphatase, Lyp, and its role in the Bcr-Abl signal transduction pathway. The Journal of biological chemistry. . 2003; 278(30): 27413-20.
Hofmann WK, Komor M, Wassmann B, Jones LC, Gschaidmeier H, Hoelzer D, Koeffler HP, Ottmann OG Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia. Blood. . 2003; 102(2): 659-61.
Mori N, Morosetti R, Mizoguchi H, Koeffler HP Progression of myelodysplastic syndrome: allelic loss on chromosomal arm 1p. British journal of haematology. . 2003; 122(2): 226-30.
Kumagai T, O'Kelly J, Said JW, Koeffler HP Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst. 2003; 95(12): 896-905.
Asou H, Gombart AF, Takeuchi S, Tanaka H, Tanioka M, Matsui H, Kimura A, Inaba T, Koeffler HP Establishment of the acute myeloid leukemia cell line Kasumi-6 from a patient with a dominant-negative mutation in the DNA-binding region of the C/EBPalpha gene. Genes Chromosomes Cancer. 2003; 36(2): 167-74.
Takeuchi S, Takeuchi N, Fermin AC, Taguchi H, Koeffler HP Frameshift mutations in caspase-5 and other target genes in leukemia and lymphoma cell lines having microsatellite instability. Leuk Res. 2003; 27(4): 359-61.
Zang C, Wachter M, Liu H, Posch MG, Fenner MH, Stadelmann C, von Deimling A, Possinger K, Black KL, Koeffler HP, Elstner E Ligands for PPARgamma and RAR cause induction of growth inhibition and apoptosis in human glioblastomas. J Neurooncol. 2003; 65(2): 107-18.
Takeuchi S, Takeuchi N, Tsukasaki K, Fermin AC, De Vas S, Seo H, Koeffler HP Mutations in the retinoblastoma-related gene RB2/p130 in adult T-cell leukaemia/lymphoma. Leuk Lymphoma. 2003; 44(4): 699-701.
Koeffler HP Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res. 2003; 9(1): 1-9.
Kaeferstein A, Krug U, Tiesmeier J, Aivado M, Faulhaber M, Stadler M, Krauter J, Germing U, Hofmann WK, Koeffler HP, Ganser A, Verbeek W The emergence of a C/EBPalpha mutation in the clonal evolution of MDS towards secondary AML. Leukemia. 2003; 17(2): 343-9.
O'Kelly J, Koeffler HP Vitamin D analogs and breast cancer. Recent Results Cancer Res. 2003; 164: 333-48.
Weisbart RH, Miller CW, Chan G, Wakelin R, Ferreri K, Koeffler HP Nuclear delivery of p53 C-terminal peptides into cancer cells using scFv fragments of a monoclonal antibody that penetrates living cells. Cancer letters. . 2003; 195(2): 211-9.
Tanosaki S, Ikezoe T, Heaney A, Said JW, Dan K, Akashi M, Koeffler HP Effect of ligands of nuclear hormone receptors on sodium/iodide symporter expression and activity in breast cancer cells. Breast cancer research and treatment. . 2003; 79(3): 335-45.
Tong X, Xie D, Roth W, Reed J, Koeffler HP NADE (p75NTR-associated cell death executor) suppresses cellular growth in vivo. International journal of oncology. . 2003; 22(6): 1357-62.
Gery S, Koeffler HP Repression of the TMEFF2 promoter by c-Myc. Journal of molecular biology. . 2003; 328(5): 977-83.
Gery S, Yin D, Xie D, Black KL, Koeffler HP TMEFF1 and brain tumors. Oncogene. . 2003; 22(18): 2723-7.
Gombart AF, Kwok SH, Anderson KL, Yamaguchi Y, Torbett BE, Koeffler HP Regulation of neutrophil and eosinophil secondary granule gene expression by transcription factors C/EBP epsilon and PU.1. Blood. . 2003; 101(8): 3265-73.
Mori N, Yang R, Kawamata N, Miller CW, Mizoguchi H, Koeffler HP Absence of R24C mutation of the CDK4 gene in leukemias and solid tumors. International journal of hematology. . 2003; 77(3): 259-62.
de Vos S, Krug U, Hofmann WK, Pinkus GS, Swerdlow SH, Wachsman W, Grogan TM, Said JW, Koeffler HP Cell cycle alterations in the blastoid variant of mantle cell lymphoma (MCL-BV) as detected by gene expression profiling of mantle cell lymphoma (MCL) and MCL-BV. Diagnostic molecular pathology : the American journal of surgical pathology, part B. . 2003; 12(1): 35-43.
de Vos S, Hofmann WK, Grogan TM, Krug U, Schrage M, Miller TP, Braun JG, Wachsman W, Koeffler HP, Said JW Gene expression profile of serial samples of transformed B-cell lymphomas. Laboratory investigation; a journal of technical methods and pathology. . 2003; 83(2): 271-85.
Takeuchi S, Tsukasaki K, Bartram CR, Seriu T, Zimmermann M, Schrappe M, Takeuchi N, Park S, Taguchi H, Koeffler HP Long-term study of the clinical significance of loss of heterozygosity in childhood acute lymphoblastic leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. . 2003; 17(1): 149-54.